Surprising connections between DNA binding and function for the near-complete set of yeast transcription factors [RNA-seq]

DNA sequence-specific transcription factors (TFs) modulate transcription and chromatin architecture, acting from regulatory sites in enhancers and promoters of eukaryotic genes. How TFs locate their DNA targets and how multiple TFs cooperate to regulate individual genes is still unclear. Most yeast TFs are thought to regulate transcription via binding to upstream activating sequences, situated within a few hundred base pairs upstream of the regulated gene. While this model has been validated for individual TFs and specific genes, it has not been tested in a systematic way with the large set of yeast TFs. Here, we have integrated information on the binding and expression targets for the near-complete set of yeast TFs. While we found many instances of functional TF binding sites in upstream regulatory regions, we found many more instances that do not fit this model. In many cases, we find that rapid TF depletion affects gene expression where there is no detectable binding of that TF to the upstream region of the affected gene. We also found that, for most TFs, only a small fraction of bound TFs regulates the nearby gene, showing that TF binding does not automatically correspond to regulation of the linked gene. Overall, our comprehensive mapping of TF binding and regulatory targets have both confirmed known TF relationships and revealed surprising properties of TF function.DNA序列特异性转录因子（DNA sequence-specific transcription factors, TFs）能够调控转录过程与染色质结构，通过结合真核基因增强子与启动子区域的调控位点发挥功能。目前，转录因子如何精准定位其DNA靶标，以及多个转录因子如何协同调控单个基因的表达，仍是尚未阐明的科学问题。既往研究认为，多数酵母转录因子通过结合靶基因上游数百碱基对范围内的上游激活序列来调控转录。尽管该模型已在单个转录因子与特定基因的研究中得到验证，但尚未针对完整的酵母转录因子集合开展系统性检验。本研究整合了近乎完整的酵母转录因子集合的结合靶标与表达靶标相关信息。我们不仅在上游调控区域中发现了大量功能性转录因子结合位点，还观测到更多不符合该经典模型的案例。在诸多情形中，即便受影响基因的上游区域未检测到对应转录因子的结合，快速转录因子耗竭仍会改变该基因的表达水平。此外，我们发现，对于多数转录因子而言，仅有极小一部分结合的转录因子会调控其邻近基因，这表明转录因子的DNA结合事件并不必然对应其连锁基因的表达调控。总体而言，我们对转录因子结合与调控靶标的全面图谱绘制，既验证了已知的转录因子调控关系，也揭示了转录因子功能中诸多出人意料的新特性。